volasertib (NBL-001) / Boehringer Ingelheim, Oncoheroes, Notable Labs - LARVOL DELTA

Detergent selection as a determinant of protein melting behavior and drug-target interaction-calling in thermal stability proteomics. (PubMed, bioRxiv) - "Performing the PISA melt in DDM versus NP-40 results in the gain and loss of distinct drug-target interactions for both the PAK4 inhibitor PF-3758309 and the PLK1 inhibitor volasertib. We further introduce a four-parameter logistic model of protein melting to aid in modeling of these findings and a linear regression framework for PISA hit calling that outperforms pairwise t-tests in low-replicate settings. Together, these results establish detergent selection as a tunable experimental variable in thermal profiling and suggest that some drug-target engagements previously attributed exclusively to intact-cell context may be recoverable in lysates with appropriate buffer conditions."

Journal

PLK1 inhibition enhances Brentuximab vedotin efficacy in CD30-positive T-cell lymphoma via spindle assembly checkpoint activation. (PubMed, Leukemia) - "Among them, volasertib consistently enhanced BV-induced cytotoxicity across multiple CD30-positive PTCL cell lines. Importantly, the combination significantly suppressed tumor growth and prolonged survival in both cell line-derived and patient-derived xenograft (PDX) models. These findings underscore the therapeutic potential of combining BV with PLK1 inhibition, and highlight SAC activation as a key mechanism to overcome therapeutic resistance in CD30-positive PTCL."

Journal • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8

Inhibition of Plk1 Attenuates Downregulation of Water and Sodium Transporters in Obstructive Nephropathy. (PubMed, Kidney Dis (Basel)) - "Plk1 function was inhibited pharmacologically using BI6727 or genetically using heterozygous Plk1 knockout mice...These findings indicate that Plk1 contributes to the maladaptive downregulation of renal water and sodium transporters during obstruction. Pharmacological inhibition or genetic reduction of Plk1 preserves transporter expression, highlighting the Plk1-cPLA2-PGE2-NEDD4/NEDD4L axis as a potential therapeutic target for correcting water and sodium imbalance in obstructive nephropathy."

Journal • Renal Disease • Targeted Protein Degradation • NEDD4 • PLK1 • TGFB1

A tailored in vivo CRISPR screen identifies BAP1 as a potent tumor suppressor of sarcoma. (PubMed, JCI Insight) - "Pharmacologic inhibition of PLK1 with volasertib significantly suppressed tumor growth in both syngeneic and autochthonous mouse models. Moreover, combining PLK1 inhibition with anti-PD-1 therapy enhanced tumor control and improved survival compared with either treatment alone. Together, these results identify PLK1 as a potential therapeutic vulnerability in BAP1-deficient sarcomas and support further evaluation of combined PLK1 inhibition and immune checkpoint blockade as a treatment strategy for a subset of STS."

IO biomarker • Journal • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • BAP1

DREAM and RB deficiency confers resistance to inhibition of mitosis (EACR 2026) - "Introduction: Mitotic inhibitors such as the PLK-1 inhibitor volasertib are promising candidates for cancer therapy... Our work reveals that loss of LIN37/DREAM promotes resistance to mitotic inhibition by allowing endoreplication. Loss of RB alone does not confer resistance but can improve it in LIN37/DREAM-deficient cells. Further, we show that resistance arises from mitotic skipping, a process that prevents cells from entering mitosis and allows them to progress to the next cell cycle round, ultimately resulting in polyploidy."

PLK1

CELL CYCLE–FOCUSED CHEMICAL SCREEN REVEALS MITOTIC KINASE INHIBITORS THAT ENHANCE THE EFFICACY OF A CD30-TARGETED ANTIBODY–DRUG CONJUGATE (EHA 2026) - "Background Brentuximab vedotin (BV), an antibody–drug conjugate (ADC) composed of an anti-CD30 monoclonal antibody conjugated to the microtubule-disrupting drug monomethyl auristatin E (MMAE), is widely used as a key therapeutic agent for the treatment of peripheral T-cell lymphoma (PTCL)...Results The screen identified three compounds—volasertib, GSK461364, and onvansertib—that exhibited strong synergy with BV in both cell lines...Summary/Conclusion Our findings highlight the therapeutic potential of combining BV with PLK1 inhibitors—particularly volasertib—as a rational strategy to enhance cytotoxicity in CD30-positive PTCL. This study provides a mechanistic and preclinical foundation for future clinical evaluation of this combination therapy."

ADC • Clinical • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • CASP3 • CCNB1 • TNFRSF8

THERAPEUTIC EFFECT OF TARGETING CASEIN KINASE II / PLK1 ONCOGENIC SIGNALING IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2026) - "(F-J) Spleen image (F), Spleen weights (G), % of human CD45 and CD7 positive T-ALL cells in the spleens (H) and bone morrow (I) and the survival (J) after T-ALL patient derived mouse model treated with Volasertib, CX-4945 and the combination for 28 days. *** P<0.001."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD7 • IKZF1 • PLK1 • PTPRC

FUNCTIONAL CONSEQUENCES OF TP53 LOSS ACROSS MAJOR IGH TRANSLOCATION SUBTYPES IN MULTIPLE MYELOMA (EHA 2026) - "In t(11; 14) t(11; 14) , TP53 loss conferred resistance to bortezomib and selinexor, but marked sensitivity to the PLK1 inhibitor volasertib, indicating cell cycle-related vulnerabilities. Conversely, TP53 loss in t(14; 16) t(14; 16) was linked to melphalan resistance, but enhanced response to bortezomib and lenalidomide/dexamethasone. Summary/Conclusion Loss of TP53 in MM does not result in a uniform biological or therapeutic phenotype but instead drives distinct molecular, functional and drug-response programs determined by IGH translocation subtype. These findings provide mechanistic insight into the heterogeneity of TP53 -altered MM and support the development of genetically informed, translocation-adapted therapeutic strategies for high-risk disease."

Hematological Malignancies • Multiple Myeloma • Oncology • CCND1 • IGH • TP53

Identification of novel therapeutic agents using patient-derived organoids in HCC (EASL 2026) - "Among them, dinaciclib, homoharringtonine, volasertib, mocetinostat, and daunorubicin, have bene already reported as effective on HCC...Among standard treatments, only sorafenib inhibited HCC-PDOs...In keeping with this, osimertinib, another drug highlighted by the screening on HCC-PDO and currently used for EGFR-mutant lung cancer, has been reported as effective also in HCC (J... The identification of dinaciclib and homoharringtonine as potent agents aligns with recent literature on novel HCC drugs, and validates the robustness of our approach and the potential of our results. Moreover, our results disclosed a significant potential for some drug repurposing. A recent study showed that cerinitib, a drug targeting ALK mutation in advanced non-small cell lung cancer, inhibits β-catenin mutated HCC via non-canonical WNT pathway independent of ALK (J Hep Reports, 2025)."

Clinical • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • ALK • CTNNB1 • EGFR

Chemoimmunotherapeutic sealants for postsurgical adjuvant therapy of malignant tumors. (PubMed, J Control Release) - "Herein, we report a chemoimmunotherapeutic fibrin sealant (CI-sealant) as a new postsurgical adjuvant therapy that converts the surgical cavity into an in situ "drug-immune depot" with localized release of immunogenic docetaxel/volasertib dual-drug nanocombo (iNCombo) and galunisertib, a TGF-β inhibitor that relieves immune suppression. Post-surgery adjuvant therapy with CI-sealant significantly prevents tumor recurrence in both murine 4 T1-Luc breast tumor and B16F10 melanoma models. This chemoimmunotherapeutic sealant opens a promising strategy for postsurgical adjuvant therapy of malignant tumors."

Journal • Breast Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • TGFB1

All Screens Lead to Polo-like kinase 1: A Central Node in Cancer Therapeutics and Resistance. (PubMed, Pharmacol Res) - "Emerging evidence supports synergistic potential of new-generation PLK1 inhibitors, such as Onvansertib, with chemo- and immune-therapies. This mini-review and perspective present current insights on PLK1 overexpression and its mechanistic impact on cancer aggressiveness and therapy resistance. We highlight the need for refined patient stratification and innovative combination regimens to exploit PLK1 inhibition in cancer treatment."

Journal • Review • Oncology • PLK1

Dual targeting of PLK1 and NOTCH signaling synergistically suppresses melanoma progression (SID 2026) - "Treatment of melanoma spheroids with PLK1 inhibitors volasertib (V, 5-25nM) or onvansertib (O, 25-100nM) alone or in combination with NOTCH inhibitor MK-0752 (M, 50-200µM) significantly reduced spheroid proliferation with combination treatment as compared to monotherapies. Interestingly, 101 proteins at ≥;1.5| fold change were solely significant in O-M group as compared to individual treatments, many of which were associated with metabolic pathways. Overall, our data suggests that PLK1 and NOTCH combination could be used as a promising approach for melanoma management."

Melanoma • Solid Tumor • PLK1 • PTEN

Investigating FOXC2-dependent mechanisms regulating stem cell Identity in breast cancer (AACR 2026) - "Pharmacologic PLK1 inhibition (Volasertib) reduces FOXC2 protein levels, and this loss is reversed by the proteasome inhibitor MG132, suggesting that PLK1-dependent phosphorylation stabilizes FOXC2...Live-cell imaging further indicates that FOXC2 is spatially regulated during mitosis and that phosphorylation may affect its chromatin association and inheritance. Collectively, our findings suggest PLK1-dependent phosphorylation of FOXC2 may stabilize the FOXC2 protein and influence its function during mitosis and regulate stem cell identity in daughter cells during cell division."

Breast Cancer • Embryonal Tumor • Oncology • Solid Tumor • Triple Negative Breast Cancer • FOXC2

Defining cancer initiating cells and their vulnerabilities in renal cell carcinoma (AACR 2026) - "Pharmacological blockade of PLK1 with Volasertib elicited dose-dependent inhibitory effect on spheroid and colony formation, with in-vivo validation showing that blocking PLK1 significantly delayed tumor growth and more efficiently prevented tumor formation in nude mice...Targeting PLK1 disrupts the fundamental self-renewal and tumor-initiating capacities of ccRCC, offering a promising avenue for therapeutic intervention through PLK1 inhibition. Furthermore, our data uncover novel and non-canonical functions for PLK1, which upon further characterization may open new ways for combinational therapeutic strategies involving PLK1 and its effectors with standard of care in advanced ccRCC."

Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • FOXM1

Targeting PLK1 or WEE1 uncovers a therapeutic vulnerability in BRCA1/2 wild-type, homologous recombination-proficient high-grade serous ovarian cancer (AACR 2026) - "We aimed to determine whether inhibition of PLK1 or WEE1, two G2/M checkpoint kinases, could uncover a therapeutic vulnerability in BRCA-WT/HRP HGSOC. We evaluated the effects of the PLK1 inhibitor volasertib and the WEE1 inhibitor adavosertib in BRCA-WT/HRP (and BRCA-mutant/HR-deficient (HRD) ovarian cancer models. BRCA-WT/HRP HGSOC exhibits distinct susceptibility to PLK1 or WEE1 inhibition through disruption of HR repair and mitotic regulation, revealing a DNA repair-based vulnerability not observed in BRCA-mutant/HRD tumors. These findings provide a strong rationale for biomarker-guided development of PLK1 or WEE1 inhibitors as therapeutic strategies for HRP ovarian cancers, a patient population with significant unmet clinical needs."

High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • PLK1 • RAD51 • TP53BP1

YF550 is a potent and selective inhibitor of KIF18A, specifically targeting CIN+ cancer cells (AACR 2025) - "In contrast to the Eg5 inhibitor Ispinesib, YF550 does not inhibit normal PBMC proliferation...YF550 has demonstrated synergistic effects when combined with various agents, including Olaparib (PARP inhibitor), PF-07104091 (CDK2 inhibitor), Elimusertib (ATR inhibitor), Volasertib (PLK1 inhibitor), and MMAE, in cellular proliferation assays. In the OVCAR3 ovarian cancer xenograft model, YF550 has shown superior efficacy compared to KIF18A inhibitor AMG650 at a 5 mg/kg dose, with no significant impact on body weight. Furthermore, YF550 induced tumor regression in both the OVCAR8 ovarian and JIMT-1 HER2 positive breast cancer xenograft models. YF550 exhibits superior ADME and PK property suitable for clinical development for CIN+ cancers with high aneuploidy score and has the potential for combination therapy with PD-1/L1 antibodies, PARP1 inhibitors, and MMAE based ADC."

IO biomarker • Late-breaking abstract • Breast Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • KIF18A

Poor radiation sensitivity and potential radiosensitizers for betel-nuts related head and neck squamous cell carcinoma in Taiwan (AACR 2024) - "Purpose & Polo-like kinase 1 inhibitor(volasertib), gluconate(blocking citrate transport & glucose metabolism), IAP inhibitor(Debio1143), glutaminase 1 inhibitor(CB839) were tested on TW2.6 to evaluate synergistic effects with radiation. In Taiwan, patients with R/M HNSCC progressing within 3 months after CCRT could be rescued by early ICIs. Recently, sequential CCRT followed by ICI or Debio-1143 with CCRT showed potential survival benefits. In our studies, novel agents such as PLK inhibitor, gluconate, and CB839 had even better radiosensitization compared with Debio1143."

IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ARID1B • ATM • BCL2 • CCND3 • CDK1 • CDK12 • DDR2 • EPHB1 • FAT1 • FGF10 • FLCN • HRAS • MITF • PDGFRB • PD-L1 • PIK3CA • PLK1 • RICTOR • SDHA • SOX9 • STK11 • TERT • TMB • TNFAIP3 • TP53

VGLL1-derived peptides demonstrated anticancer effect by inhibiting VGLL1-TEAD4 interaction (AACR 2024) - "We also found that SCVP in combination and the PLK inhibitor volasertib resulted in a synergistic effect on the growth inhibition of breast cancer cells. In conclusion, we demonstrated VGLL1 as a novel target for anticancer drug development, and elucidated the molecular mechanism and therapeutic potential of the SCVP in gastric and breast cancers."

Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCND1 • EGFR • HER-2 • IGFBP3 • IGFBP5 • MMP9 • PLK1 • RPS6KA3 • TEAD1 • TEAD4 • TGFB1 • ZNF292

PLK1 inhibition as a novel therapeutic strategy in HER2+ breast cancer with germline METN375S mutation (AACR 2025) - "Our findings suggest that METN375S variant promotes tumorigenesis by hyperactivating HER2 signaling and enhancing PLK1 pathway. These findings highlight the potential of PLK1 inhibitors, as a novel therapeutic option for METN375S mutant HER2+ BC and supports further evaluation of PLK-1 in HER2+ BC."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • HER-2

Ovarian cancer treatments: Using HSF1 and MYC gene amplification as a biomarker (AACR 2025) - "We show that loss of HSF1 and MYC decrease proliferation and colony formation ability of ovarian cancer cells using knockdown siRNAs and that the Volasertib and Entinostat inhibitors are more effective in treating ovarian cancers that carry amplifications of HSF1 and MYC than those with other driver amplifications. Work with both Volasertib and Entinostat aim to show that amplifications of oncogenes in high-grade serous ovarian cancer can be used as a biomarker for new treatment strategies in ovarian cancer."

Biomarker • Gynecologic Cancers • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCNE1 • HSF1 • KRAS • MYC

Novel combinational therapeutic strategy in angiosarcoma through PLK1 and mTOR co-inhibition (AACR 2025) - "In the current study, we observed a synergistic combination of PLK1 inhibition by Volasertib and mTOR inhibition by Rapamycin in AS in vitro and in vivo. Our objective is to determine the mechanisms and pathways governing the development and progression of AS to generate novel precision-targeted therapies. Our findings conclude that PLK1 is a viable therapeutic target in AS, and the combined inhibition of PLK1 and mTOR represents a promising novel therapeutic strategy for this aggressive cancer."

Angiosarcoma • Oncology • Sarcoma • Solid Tumor • PLK1

PLK1 predicts aggressive behavior in CRC patients and its inhibition reverse chemoresistance in CRC cells (AACR 2024) - "To explore the role of PLK1 on chemoresistance, we inhibited PLK1 using specific inhibitor, volasertib and we showed that volasertib effectively reversed 5-Fu resistance in these cells...In addition, we showed that silencing of ERK1/2 reversed the chemoresistance, EMT and stemness of PLK1 expressing CRC cell lines. Our findings underscore the significant role of PLK1 in conferring chemoresistance, and targeting PLK1 could represent a viable therapeutic approach for the treatment of patients with an aggressive subtype of CRC."

Clinical • Colorectal Cancer • Microsatellite Instability • Oncology • MSI • PLK1 • ZEB1

Cyclin E1 overexpression as a predictive biomarker for PLK1 and WEE1 inhibitor efficacy in ovarian cancer (AACR 2025) - "Twelve ovarian cancer cell lines (5 high-grade serous [HGSOC], 5 clear cell [CCOC], and 2 endometrioid [EOC] ovarian carcinomas) were treated with the PLK1 inhibitor volasertib and the WEE1 inhibitor adavosertib to evaluate drug sensitivity, cell cycle effects, and apoptosis in vitro, as well as tumor growth in vivo. Both inhibitors induced cleaved PARP and γH2AX in high Cyclin E1-expressing tumors but not in low-expression models. Cyclin E1 overexpression, regardless of TP53 status, may serve as a predictive biomarker for the efficacy of these inhibitors, thereby offering potential personalized treatment strategies for ovarian cancer."

Biomarker • Clinical • Oncology • Ovarian Cancer • Solid Tumor • CCNE1 • PLK1 • TP53

Guided by a predictive ex vivo test: Bringing the PLK1 inhibitor volasertib back into the clinic for venetoclax-HMA relapsed/refractory acute myeloid leukemia patients (AACR 2024) - "INTRODUCTION: Volasertib, a polo-like kinase 1 (PLK1) inhibitor, has a roughly 30% CR/CRi response rate in de novo acute myeloid leukemia (AML) patients when combined with low-dose cytarabine. Volasertib's EC50 values clustered within a narrow range, suggesting that EC50 may not be a suitable metric to stratify patients into responders and nonresponders, in contrast to AUCs and residual blast fractions at 31.6 and 100 nM of volasertib, which displayed more heterogeneous distributions. Limitations include small sample sizes, especially for the R/R group."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

The co-targeting of PLK1 and FoxM1 contributes to synergistic antitumor effects in PTC (AACR 2024) - "The combined inhibition of PLK1 with volasertib and FoxM1 with thiostrepton synergistically attenuated PTC cell growth in vitro and in vivo. Our findings suggest that co-targeting of PLK1 and FoxM1 could be a viable therapeutic strategy for treating patients with an aggressive subtype of PTC."

Oncology • FOXM1 • PLK1